chr19-47320459-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001736.4(C5AR1):c.682C>T(p.Arg228Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,612,786 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
C5AR1
NM_001736.4 missense
NM_001736.4 missense
Scores
5
5
9
Clinical Significance
Conservation
PhyloP100: 0.0370
Genes affected
C5AR1 (HGNC:1338): (complement C5a receptor 1) Enables G protein-coupled receptor activity and complement component C5a receptor activity. Involved in several processes, including complement component C5a signaling pathway; mRNA transcription by RNA polymerase II; and positive regulation of ERK1 and ERK2 cascade. Located in apical part of cell and basolateral plasma membrane. Biomarker of Alzheimer's disease; asthma; chronic obstructive pulmonary disease; rhinitis; and severe acute respiratory syndrome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
C5AR1 | NM_001736.4 | c.682C>T | p.Arg228Trp | missense_variant | 2/2 | ENST00000355085.4 | NP_001727.2 | |
C5AR1 | XM_047439300.1 | c.784C>T | p.Arg262Trp | missense_variant | 3/3 | XP_047295256.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
C5AR1 | ENST00000355085.4 | c.682C>T | p.Arg228Trp | missense_variant | 2/2 | 1 | NM_001736.4 | ENSP00000347197 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152162Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250480Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135440
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GnomAD4 exome AF: 0.0000253 AC: 37AN: 1460624Hom.: 0 Cov.: 79 AF XY: 0.0000317 AC XY: 23AN XY: 726662
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152162Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74330
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2024 | The c.682C>T (p.R228W) alteration is located in exon 2 (coding exon 2) of the C5AR1 gene. This alteration results from a C to T substitution at nucleotide position 682, causing the arginine (R) at amino acid position 228 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at